Our ultimate aim is to predict hormone dependency of prostate cancers by measurement of cytosol receptor and/or endogenous DHT and prostatic acid phosphatase in a prostate biopsy. The biologically differentiated prostate has been shown to contain the following 5 major androgen metabolites: testosterone (T); dihydrotestosterone (DHT); androstanedione; delta 4-androstenedione (delta-4A); and androstanediols (A-diols). It is our hypothesis that quantitative amounts of DHT, the most important androgen metabolite present in the prostate, should depend upon plasma testosterone, 5 alpha-reductase, specific cytosol receptor protein and nuclear acceptor. Levels of other androgen metabolites, less important, will depend upon appropriate oxidative and reductive enzymes. The level of prostatic acid phosphatase (PAP) in prostate cancer would serve as an indicator for the integrity of the translational component of protein synthesis which is largely regulated by androgens in normal prostate tissue. By contrast, undifferentiated prostate cancers may lack either the cytosol receptor and/or one or more of the androgen metabolizing enzymes. Levels of PAP, if concordant with receptor and/or DHT levels, should provide stronger evidence for the state of differentiation than the androgen mediating biochemical steps alone. To detect and quantitate human prostate cytosol receptor, cytosol will be precipitated with protamine sulfate to separate it from TeBG. The androgen metabolites will then be separated and quantitated by radioimmunoassay. A modified method for the quantitative measurements of DHT and radioimmunoassay of PAP in a 50 mg biopsy of prostate tissue has been developed. This method will be applied to biopsy specimens from previously untreated patients with stage III or stage IV prostate cancer and the clinical course of the patients will be correlated with the biopsy DHT level prior to treatment. Histologic grading will also be compared to DHT levels as a predictor of clinical responsiveness to antiandrogens. For patients previously treated with castration and/or estrogen who have low plasma testosterone levels, cytosol receptor will be measured to evaluate tumor differentiation.